16 TOTAL SYNTHESES OF HAEMANTHAMINE,HAEMANTHIDINE,AND TAZETTINE : APPLICATION OF 4,5-DIOXO-Δ^2-PYRROLINES TO ALKALOID SYNTHESES
Details
Several 3-Aryl-4, 5-dioxo-Δ^2-pyrrolines were newly synthesized and found to be a sufficient dienophile to prepare angularly substituted cis-fused hydro-indoles. The method thus opened the way to synthesize various natural alkaloids having spiro-structure. By application of this method, the title alkaloids were synthesized as follows. Starting from piperonyl cyanide the key intermediate (14) was prepared by 3 steps via controlled hydrogenation (40Kg/cm^2 and 70°) of cyanopyruvate (10). Treatment of (14) by NBA, then with base afforded epoxy-ketone (33) which on BF_3-etherate in methanol gave (34) as a major product. LAH reduction of (34) gave stereospecifically a diol (36), which is common intermediate of the title alkaloids. Pictet-Spengler cyclization of (36) by HCHO-AcOH yielded (37) which on tosylation and detosylation with DBU gave (±)-haemanthamine (42). Bischler-Napieralsky reaction of the formate (43) by POCl_3 gave 6-hydroxy derivative (44) which on methylation followed by alkaline treatment gave (45). Tosylation and detosylation of (45) gave (±)-tazettine (46). While (44) was smoothly oxidized by MnO_2 to a lactam which could be converted to (47) as above. Short reduction of (47) with LAH gave (±)-haemanthidine (48). The identities of the synthetic specimens were confirmed by comparisons of i.r. and n.m.r. spectra, and t.l.c. with natural alkaloids.
